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Ilaria Barone, Elena Novelli, Enrica Strettoi; Long-term effects of Environmental Enrichment (EE) on a mouse model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2578.
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© ARVO (1962-2015); The Authors (2016-present)
In mouse models of typical Retinitis Pigmentosa (RP), rod death is accompanied and followed by secondary degeneration of cones. Enviromental Enrichment (EE) consists in the exposure to a combination of complex motor, inanimate and social stimuli. EE is an experimental paradigm that prolongs neuronal survival, slows down neuronal degeneration, enhances plasticity and neurotrophic factor production throughout the CNS. In previous studied we showed that EE delays photoreceptor death and preserves visual structure and function in rd10 mutant mice (a model of RP) up to 90 days of age. Here, we assess the effects of EE on the same mutants, kept in the same environment, up to 1 year of age. We focus on the morphology and survival of cones and on visual function in photopic conditions.
Animals were treated in accordance with ARVO and institutional guidelines. rd10 mice (homozygous for the rod-specific phosphodiesterase mutation, C57BL/6J-Pde6brd10/J mice), were conceived, born and maintained in enriched conditions up to 1 year of age. Retinal morphology, photoreceptor survival and visual behaviour were assessed on a group of 4 mice at 1 year of age, and compared to those of age-matched rd10 mice, kept in standard laboratory conditions(ST). Morphological studies were done with retinal cell type specific antibodies, confocal microscopy and morphometric analysis of retinal whole mounts and histological sections. Visual acuity was assessed in photopic conditions by means of a visual water maze adapted by Prusky.
Albeit a continue decline in the number of cones with time, EE rd10 mice of 1 year show almost three times as many surviving cones than ST controls (34,000±4,000 vs 12,700± 1,800; t-test; **p=0.003). The morphology of individual cones in EE mice is better preserved as well, as shown by more numerous and longer outer segments. Behaviour-based tests show that the same EE mice preserve a residual acuity of 0.138 cycles/degree. On the contrary, virtually all age-matched rd10 ST controls are uncapable to perform the visual task (0.138±0 vs 0.063±0.014 t-test *p=0.029).
Early and prolonged exposure of RP mutant mice to Environmental Enrichment preserves cones even in the long run. A minimal visual acuity is also maintained. This experimental paradigm migth be exploited for developing non invasive strategies to delay vision loss in RP individuals, also in perspective of treatments requiring cone viability.
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